Priming neuromodulation for faster therapeutic response

ABSTRACT

An example a system includes a neuromodulation generator that may be configured to use electrodes to generate a first modulation field over a test region of neural tissue along the electrodes to prime the neural tissue throughout the test region and a second modulation field to test targeted locations within the test region for therapeutic effectiveness. A memory may be configured to store a first modulation field parameter for generating the first modulation field and a second modulation field parameter set for generating the second modulation field to modulate a targeted location within the test region. The second modulation field parameter set is programmable for modulating other targeted locations. The controller may be configured to control the neuromodulation generator to use the first modulation field parameter set to deliver the first modulation field and to use the second modulation field parameter set to deliver the second modulation field.

CLAIM OF PRIORITY

This application is a continuation of U.S. application Ser. No.15/141,075, filed Apr. 28, 2016, which claims the benefit of priority toU.S. Provisional Patent Application Ser. No. 62/294,762, filed on Feb.12, 2016 and U.S. Provisional Patent Application Ser. No. 62/154,556,filed Apr. 29, 2015, each of which is incorporated herein by referencein its entirety.

TECHNICAL FIELD

This document relates generally to medical devices, and moreparticularly, to systems, devices and methods for deliveringneuromodulation.

BACKGROUND

Neuromodulation (or “neural modulation”, also referred to as“neurostimulation” or “neural stimulation”) has been proposed as atherapy for a number of conditions. Often, neuromodulation and neuralstimulation may be used interchangeably to describe excitatorystimulation that causes action potentials as well as inhibitory andother effects. Examples of neuromodulation include Spinal CordStimulation (SCS), Deep Brain Stimulation (DBS), Peripheral NerveStimulation (PNS), and Functional Electrical Stimulation (FES). SCS, byway of example and not limitation, has been used to treat chronic painsyndromes.

Conventional SCS delivers electrical pulses to the spinal cord, maskingthe transmission of pain signals to the brain. While these electricalpulses can reduce pain, they are often associated with possibleunpleasant tingling and buzzing sensations known as paresthesia.

Sub-perception SCS therapy has been proposed to provide pain reliefwithout the accompanying paresthesia. However, the wash-in time forsub-perception SCS therapy is significant. The wash-in time refers to atime from the start of a therapy to when a therapeutic response to thetherapy can be observed. Since there typically is no immediate feedbackfor a sub-perception SCS, it can be a challenge to find a desirable oroptimal location (sweet-spot) for the modulation field within an officevisit.

SUMMARY

An example (e.g., “Example 1”) of a system includes an electrodearrangement, a neuromodulation generator, a memory, and a controller.The neuromodulation generator may be configured to use electrodes in theelectrode arrangement to generate modulation fields including a firstmodulation field over a test region of neural tissue along the electrodearrangement to prime the neural tissue throughout the test region, and asecond modulation field to test a plurality of targeted locations ofneural tissue within the test region for therapeutic effectiveness. Thememory may be configured to store a first modulation field parameter setfor use to generate the first modulation field, and a second modulationfield parameter set for use to generate the second modulation field tomodulate one of the plurality of the targeted locations within the testregion. The second modulation field parameter set is programmable tochange the second modulation field to modulate other ones of theplurality of targeted locations. The controller may be configured tocontrol the neuromodulation generator to use the first modulation fieldparameter set to prime the test region with the first modulation fieldand to use the second modulation field parameter set to deliver a secondmodulation field to modulate the one of the targeted locations withinthe test region.

In Example 2, the subject matter of Example 1 may optionally beconfigured such that the neuromodulation generator is configured to useelectrodes in the electrode arrangement to generate at least onesub-perception modulation field, and at least one of the firstmodulation field and the second modulation field is the sub-perceptionmodulation field.

In Example 3, the subject matter of Example 1 may optionally beconfigured such that the neuromodulation generator is configured to useelectrodes in the electrode arrangement to generate at least onesupra-perception modulation field, and at least one of the firstmodulation field and the second modulation field is the supra-perceptionmodulation field.

In Example 4, the subject matter of any one or any combination ofExamples 1-3 may optionally be configured such that the controller isconfigured to generate the first modulation field to prime the testregion for a period of time before the second modulation field.

In Example 5, the subject matter of any one or any combination ofExamples 1-3 may optionally be configured such that the controller isconfigured to generate the first modulation field for at least a portionof a time when the second modulation field is generated.

In Example 6, the subject matter of any one or any combination ofExamples 1-5 may optionally be configured such that the controller isconfigured to implement a trolling routine to troll the secondmodulation field through the plurality of targeted locations within thetest region of neural tissue.

In Example 7, the subject matter of Example 6 may optionally beconfigured such that the trolling routine implemented by the controlleris configured to perform at least one of automatically moving the secondmodulation field or receiving a user-controlled trolling command tocontrol movement of the second modulation field.

In Example 8, the subject matter of Example 8 may optionally beconfigured such that the programmable second modulation field parameterset includes programmable fractionalized current values for electrodeswithin the electrode arrangement, wherein modification of theprogrammable fractionalized current values moves the second modulationfield.

In Example 9, the subject matter of any one or any combination ofExamples 6-8 may optionally be configured such that the controller isconfigured to implement a routine as the second modulation field istrolled through the plurality of targeted positions within the testregion to identify one or more therapeutically-effective locations inthe test region where the second modulation field provides pain relief,and to store in the memory the modulation field parameter data thatprovides the pain relief as the second modulation field parameter setand measures indicating therapeutic effectiveness for each location ofthe plurality of targeted positions.

In Example 10, the subject matter of Example 9 may optionally beconfigured such that the one or more therapeutically-effective locationsincludes a tested location within the test region of neural tissue thatis most effective in providing pain relief.

In Example 11, the subject matter of Example 10 may optionally beconfigured such that the neuromodulation generator is configured toprime a target region over the therapeutically-effective location anddeliver a therapeutic modulation to the therapeutically-effectivelocation.

In Example 12, the subject matter of any one or any combination ofExamples 9-11 may optionally be configured such that the routineimplemented by the controller is configured to receive a titrationsignal that indicates an instruction to adjust an intensity of thesecond modulation field, adjust the intensity in response to receivingthe titration signal, and receive an indication signal that the adjustedmodulation intensity achieved the pain relief.

In Example 13, the subject matter of Example 12 may optionally beconfigured such that the titration signal includes anautomatically-provided signal to automatically adjust the intensity ofthe second modulation field, and the system is configured to receive auser-provided command to stop the automatic adjustment of the intensityof the second modulation field.

In Example 14, the subject matter of any one or any combination ofExamples 1-13 may optionally be configured such that the controller isconfigured to use a timing channel to prime the test region and to useat least one other timing channel to generate to deliver the therapeuticmodulation.

In Example 15, the subject matter of any one or any combination ofExamples 1-14 may optionally be configured such that the system includesan implantable device and an external device. The implantable deviceincludes the neuromodulation generator, the memory and the controller.The external device and the implantable device are configured tocommunicate. The external device is configured to provide a graphicaluser interface to provide at least one of a graphical lead indicatorconfigured to indicate the test region of neural tissue or at least oneof the plurality of the targeted locations within the test region.

An example of a method (e.g., “Example 16”) is also provided. The methodmay include generating a first modulation field over a test region ofneural tissue along an electrode arrangement to prime the neural tissuethroughout the test region, and generating a second modulation field totest a plurality of targeted locations of neural tissue within the testregion for therapeutic effectiveness.

In Example 17, the subject matter of Example 16 may optionally includethat at least one of the first modulation field or the second modulationfield includes a sub-perception modulation field.

In Example 18, the subject matter of Example 16 may optionally includethat at least one of the first modulation field or the second modulationfield includes a supra-perception modulation field.

In Example 19, the subject matter of generating the first modulationfield as found in any one or any combination of Examples 16-18 mayoptionally include generating the first modulation field over the testregion of neural tissue along the electrode arrangement to prime theneural tissue throughout the test region for a period of time beforegenerating the second modulation field.

In Example 20, the subject matter of generating the first modulationfield as found in any one or any combination of Examples 16-18 mayoptionally include generating the first modulation field for at least aportion of a time when the second modulation field is generated.

In Example 21, the subject matter of any one or any combination ofExamples 16-20 may optionally further include trolling the secondmodulation field through the plurality of targeted locations within thetest region of neural tissue. The trolling includes automatically movingthe second modulation field or receiving a user-controlled trollingcommand to control movement of the second modulation field.

In Example 22, the subject matter of generating the second modulationfield as found in any one or any combination of Examples 16-21 mayoptionally include using a programmable second modulation fieldparameter set to generate the second modulation field to modulate one ofthe plurality of the targeted locations within the test region.

In Example 23, the subject matter of Example 22 may optionally furtherinclude programming different values for the programmable secondmodulation field parameter set to move the second modulation field todifferent ones of the plurality of targeted locations within the testregion of neural tissue.

In Example 24, the subject matter of Example 23 may optionally furtherinclude identifying a therapeutically-effective location being a testedlocation of the plurality of targeted locations within the test regionof neural tissue that is most effective in treating a condition using atherapeutic modulation.

In Example 25, the subject matter of Example 24 may optionally furtherinclude priming a target region over the therapeutically-effectivelocation and delivering the therapeutic modulation to thetherapeutically-effective location.

This Summary is an overview of some of the teachings of the presentapplication and not intended to be an exclusive or exhaustive treatmentof the present subject matter. Further details about the present subjectmatter are found in the detailed description and appended claims. Otheraspects of the disclosure will be apparent to persons skilled in the artupon reading and understanding the following detailed description andviewing the drawings that form a part thereof, each of which are not tobe taken in a limiting sense. The scope of the present disclosure isdefined by the appended claims and their legal equivalents.

BRIEF DESCRIPTION OF THE DRAWINGS

Various embodiments are illustrated by way of example in the figures ofthe accompanying drawings. Such embodiments are demonstrative and notintended to be exhaustive or exclusive embodiments of the presentsubject matter.

FIG. 1 illustrates a portion of a spinal cord.

FIG. 2 illustrates, by way of example, an embodiment of aneuromodulation system.

FIG. 3 illustrates, by way of example, an embodiment of a modulationdevice, such as may be implemented in the neuromodulation system of FIG.2.

FIG. 4 illustrates, by way of example, an embodiment of a programmingdevice, such as may be implemented as the programming device in theneuromodulation system of FIG. 2.

FIG. 5 illustrates, by way of example, an implantable neuromodulationsystem and portions of an environment in which system may be used.

FIG. 6 illustrates, by way of example, an embodiment of a Spinal CordStimulation (SCS) system, which also may be referred to as a Spinal CordModulation (SCM) system.

FIG. 7 illustrates, by way of example, some features of theneuromodulation leads and a pulse generator.

FIG. 8 is a schematic view of a single electrical modulation leadimplanted over approximately the longitudinal midline of the patient'sspinal cord.

FIG. 9 illustrates an embodiment where an electrical modulation lead hasbeen implanted more laterally with respect to the spinal cord, therebyplacing it proximate the dorsal horn of the spinal cord, and the otherelectrical modulation lead has been implanted more medially with respectto the spinal cord, thereby placing it proximate the dorsal column ofthe spinal cord.

FIG. 10 illustrates a schematic view of the electrical modulation leadshowing an example of the fractionalization of the anodic currentdelivered to the electrodes on the electrical modulation lead.

FIGS. 11A-11B illustrate, by way of example and not limitation,electrode arrangements and test regions of neural tissue along theelectrode arrangements.

FIGS. 12A-12C illustrate, by way of example and not limitation, neuraltissue locations that may be targeted within the test region in one, twoand three dimensions, respectively.

FIG. 13 illustrates an example of a method for finding a sweet spot forsub-perception modulation.

FIG. 14 illustrates, by way of example, aspects of a binary searchroutine as a rostra-caudal focus routine.

FIG. 15 illustrates an example of the binary search routine.

FIGS. 16A-16C illustrate, by way of example, an edge search routine.

FIG. 17 illustrates an example of a system for finding a sweet-spot forsub-perception modulation.

FIG. 18 illustrates, by way of example, and not limitation,sub-perception modulation intensity used to prime the test region and totest a therapeutic effect of locations within the test region.

FIGS. 19A-19B illustrate relative timing between the prime modulationfield and the sweet spot test session to test a therapeutic effect oflocations within the test region,

DETAILED DESCRIPTION

The following detailed description of the present subject matter refersto the accompanying drawings which show, by way of illustration,specific aspects and embodiments in which the present subject matter maybe practiced. These embodiments are described in sufficient detail toenable those skilled in the art to practice the present subject matter.Other embodiments may be utilized and structural, logical, andelectrical changes may be made without departing from the scope of thepresent subject matter. References to “an”, “one”, or “various”embodiments in this disclosure are not necessarily to the sameembodiment, and such references contemplate more than one embodiment.The following detailed description is, therefore, not to be taken in alimiting sense, and the scope is defined only by the appended claims,along with the full scope of legal equivalents to which such claims areentitled.

Sub-perception neuromodulation is neuromodulation that can betherapeutically effective, Thus, the therapeutic effects of thesub-perception neuromodulation can be perceived. However, unlikeconventional SCS therapy which can cause sensations (e.g. paresthesia)when the therapy is delivered, the energy of the deliveredsub-perception modulation field is not perceptible. That is, a patientis not able to sense when the stimulation is “on” or “off”.

Sub-perception SCS may typically have a wash-in period on the order ofabout one day. Thus, when the programmed modulation parameters arechanged to change the location of the modulation field, the patient maynot be able to determine the effect that the changes have on pain for aday or so. This make it difficult quickly titrate the modulation fieldof the sub-perception SCS to provide effective pain relief to thepatient.

Various embodiments may be used to provide a faster therapeutic response(e.g. pain relief) to the sub-perception modulation. Faster responses tosub-perception modulation may be useful in order to find an effectivelocation (sweet-spot) for the modulation field within an office visit.The sweet spot may be a relatively optimal location for the modulationfield as it is more optimal than other locations tested.

Various embodiments may deliver a low intensity field in preparation fortesting for and finding the sweet-spot for the sub-perception modulationfield. The preparatory, lower intensity field may be referred to hereinas a prime field, as it is used to prime the neural tissue to induce afaster response to the sub-perception modulation field. Thus, primingthe neural tissue enables faster pain relief feedback from the patientduring the search for the modulation field sweet spot.

While priming neural tissue for purposes of testing sub-perceptionmodulation is specifically discussed as an example, priming neuraltissue can be applied to lower the stimulation energy required for bothsub-perception modulation and supra-perception modulation, and expeditethe response to both test and therapeutic modulations. The energy of thesupra-perception modulation delivered to the modulation field isperceptible. The therapeutic modulation is delivered to treat acondition indicated for at least one type of modulation. A testmodulation includes modulation delivered for the purposes of testingeffectiveness of a therapeutic modulation and/or setting parameters forthe therapeutic modulation. For example, a patient suffering fromcertain types of pain may be indicated for spinal cord modulation as thetherapeutic modulation. A test modulation may be delivered to find thesweet spot for the modulation field and/or other parameters controllingdelivery of the therapeutic modulation. Depending on various factorssuch as patient preference and effectiveness, sub-perception modulationand/or supra-perception modulation may be delivered as the therapeuticmodulation. The target tissue of the modulation can be primed for thetest modulation and/or the therapeutic modulation. While specificallydiscussed for test modulation delivered in preparation for therapeuticsub-perception modulation, various embodiments can include applying thepriming techniques (including timing of the priming relative to thetherapeutic modulation) discussed in this document to test modulationdelivered in preparation for therapeutic sub-perception modulation, testmodulation delivered in preparation for therapeutic supra-perceptionmodulation, therapeutic sub-perception modulation, and therapeuticsupra-perception modulation.

As some embodiments described herein involve Spinal Cord Stimulation(SCS, also referred to as spinal cord modulation), a brief descriptionof the physiology of the spinal cord is provided herein to assist thereader. FIG. 1 illustrates, by way of example, a portion of a spinalcord 100 including white matter 101 and gray matter 102 of the spinalcord. The gray matter 102 includes cell bodies, synapse, dendrites, andaxon terminals. Thus, synapses are located in the gray matter. Whitematter 101 includes myelinated axons that connect gray matter areas. Atypical transverse section of the spinal cord includes a central“butterfly” shaped central area of gray matter 102 substantiallysurrounded by an ellipse-shaped outer area of white matter 101. Thewhite matter of the dorsal column (DC) 103 includes mostly largemyelinated axons that form afferent fibers that run in an axialdirection. The dorsal portions of the “butterfly” shaped central area ofgray matter are referred to as dorsal horns (DH) 104. In contrast to theDC fibers that run in an axial direction, DH fibers can be oriented inmany directions, including perpendicular to the longitudinal axis of thespinal cord. Examples of spinal nerves 105 are also illustrated,including a dorsal root (DR) 105, dorsal root ganglion 107 and ventralroot 108. The dorsal root 105 mostly carries sensory signals into thespinal cord, and the ventral root functions as an efferent motor root.The dorsal and ventral roots join to form mixed spinal nerves 105.

SCS has been used to alleviate pain. A therapeutic goal for conventionalSCS programming has been to maximize stimulation (i.e., recruitment) ofthe DC fibers that run in the white matter along the longitudinal axisof the spinal cord and minimal stimulation of other fibers that runperpendicular to the longitudinal axis of the spinal cord (dorsal rootfibers, predominantly), as illustrated in FIG. 1. The white matter ofthe DC includes mostly large myelinated axons that form afferent fibers.While the full mechanisms of pain relief are not well understood, it isbelieved that the perception of pain signals is inhibited via the gatecontrol theory of pain, which suggests that enhanced activity ofinnocuous touch or pressure afferents via electrical stimulation createsinterneuronal activity within the DH of the spinal cord that releasesinhibitory neurotransmitters (Gamma-Aminobutyric Acid (GABA), glycine),which in turn, reduces the hypersensitivity of wide dynamic range (WDR)sensory neurons to noxious afferent input of pain signals traveling fromthe dorsal root (DR) neural fibers that innervate the pain region of thepatient, as well as treating general WDR ectopy. Consequently, the largesensory afferents of the DC nerve fibers have been targeted forstimulation at an amplitude that provides pain relief. Currentimplantable neuromodulation systems typically include electrodesimplanted adjacent, i.e., resting near, or upon the dura, to the dorsalcolumn of the spinal cord of the patient and along a longitudinal axisof the spinal cord of the patient.

Activation of large sensory DC nerve fibers also typically creates theparesthesia sensation that often accompanies conventional SCS therapy.Although alternative or artifactual sensations, such as paresthesia, areusually tolerated relative to the sensation of pain, patients sometimesreport these sensations to be uncomfortable, and therefore, they can beconsidered an adverse side-effect to neuromodulation therapy in somecases.

Some embodiments deliver sub-perception therapy that is therapeuticallyeffective to treat pain, for example, but the patient does not sense thedelivery of the modulation field (e.g. paresthesia). Sub-perceptiontherapy may be provided using higher frequency modulation (e.g. about1500 Hz or above) of the spinal cord. Sub-perception modulation may alsobe provided through modulation field shaping (e.g., using multipleindependent current control, or MICC), and temporal shaping of pulsetrain (e.g., burst, longer pulses). It appears that these higherfrequencies may effectively block the transmission of pain signals inthe afferent fibers in the DC. Some embodiments herein selectivelymodulate DH tissue or DR tissue over DC tissue to provide sub-perceptiontherapy. Such selective modulation may be delivered at lowerfrequencies. For example, the selective modulation may be delivered atfrequencies less than 1,200 Hz. The selective modulation may bedelivered at frequencies less than 1,000 Hz in some embodiments. In someembodiments, the selective modulation may be delivered at frequenciesless than 500 Hz. In some embodiments, the selective modulation may bedelivered at frequencies less than 350 Hz. In some embodiments, theselective modulation may be delivered at frequencies less than 130 Hz.The selective modulation may be delivered at low frequencies (e.g. aslow as 2 Hz). The selective modulation may be delivered even withoutpulses (e.g. 0 Hz) to modulate some neural tissue. By way of example andnot limitation, the selective modulation may be delivered within afrequency range selected from the following frequency ranges: 2 Hz to1,200 Hz; 2 Hz to 1,000 Hz, 2 Hz to 500 Hz; 2 Hz to 350 Hz; or 2 Hz to130 Hz. Systems may be developed to raise the lower end of any theseranges from 2 Hz to other frequencies such as, by way of example and notlimitation, 10 Hz, 20 Hz, 50 Hz or 100 Hz. By way of example and notlimitation, it is further noted that the selective modulation may bedelivered with a duty cycle, in which stimulation (e.g. a train ofpulses) is delivered during a Stimulation ON portion of the duty cycle,and is not delivered during a Stimulation OFF portion of the duty cycle.By way of example and not limitation, the duty cycle may be about10%±5%, 20%±5%, 30%±5%, 40%±5%, 50%±5% or 60%±5%. For example, a burstof pulses for 10 ms during a Stimulation ON portion followed by 15 mswithout pulses corresponds to a 40% duty cycle.

While SCS is specifically discussed as an example of neuromodulationtherapy, various embodiments can also include applying the primingtechniques including timing of delivery discussed in this document toPeripheral Nerve Stimulation (PNS) therapies. For example,sub-perception PNS may be applied to alleviate pain. Various embodimentsinclude priming the neural tissue at target locations for delivering theneuromodulation where required intensity of the neuromodulation fortesting and/or therapeutic purposes may be lowered.

FIG. 2 illustrates an embodiment of a neuromodulation system. Theillustrated system 210 includes electrodes 211, a modulation device 212,and a programming device 213. The electrodes 211 are configured to beplaced on or near one or more neural targets in a patient. Theelectrodes 211 may form part of an electrode arrangement. The modulationdevice 212 is configured to be electrically connected to electrodes 211and deliver neuromodulation energy, such as in the form of electricalpulses, to the one or more neural targets though electrodes 211. Thedelivery of the neuromodulation is controlled using a plurality ofmodulation parameters, such as modulation parameters specifying theelectrical pulses and a selection of electrodes through which each ofthe electrical pulses is delivered. In various embodiments, at leastsome parameters of the plurality of modulation parameters areprogrammable by a user, such as a physician or other caregiver. Theprogramming device 213 provides the user with accessibility to theuser-programmable parameters. In various embodiments, the programmingdevice 213 is configured to be communicatively coupled to modulationdevice via a wired or wireless link. In various embodiments, theprogramming device 213 includes a graphical user interface (GUI) 214that allows the user to set and/or adjust values of theuser-programmable modulation parameters.

In various embodiments, the neuromodulation system 210 can includeimplantable and external elements. For example, the modulation device212 can be an implantable modulation device, the electrodes 211 caninclude electrodes in one or more implantable lead and/or theimplantable modulation device, and the programming device can be anexternal programming device configured to be communicatively coupled tothe implantable modulation device via telemetry, as further discussedwith reference to FIGS. 5 and 6. In another example, the modulationdevice 212 can be an external modulation device such as a TranscutaneousElectrical Neural Stimulation (TENS) device, the electrodes 211 caninclude surface electrodes such as skin patch electrodes, and theprogramming device can be an external programming device configured tobe communicatively coupled to the implantable modulation device via awired or wireless link, or integrated with the external modulationdevice. In still another example, the modulation device 212 can be anexternal modulation device, the electrodes 211 can include percutaneouselectrodes, and the programming device can be an external programmingdevice configured to be communicatively coupled to the implantablemodulation device via a wired or wireless link, or integrated with theexternal modulation device. In various embodiments, an externalmodulation device with surface and/or percutaneous electrodes can beused, for example, for delivering a test modulation, delivering atherapeutic modulation during a trial period, and delivering ashort-term therapeutic modulation.

In one embodiment, an external modulation device with surface electrodescan be used during a trial period prior to a potential implantation ofan implantable SCS system. A skin patch including the surface electrodesis placed over the patient's spine near the region where percutaneouselectrodes will be placed for use during the trial period. The externalmodulation device such as a dedicated External Trial Stimulator (ETC)and/or an external TENS device is used to prime the neural tissue beforethe trial period using one or more electrodes selected from the surfaceelectrodes. This allows the programming of the external modulationdevice for delivering therapeutic modulation through the percutaneouselectrodes to be performed with reduced wash-in time, such asimmediately following the placement of the percutaneous electrodes.

FIG. 3 illustrates an embodiment of a modulation device 312, such as maybe implemented in the neuromodulation system 210 of FIG. 2. Theillustrated embodiment of the modulation device 312 includes amodulation output circuit 315 and a modulation control circuit 316.Those of ordinary skill in the art will understand that theneuromodulation system 210 may include additional components such assensing circuitry for patient monitoring and/or feedback control of thetherapy, telemetry circuitry and power. The modulation output circuit315 produces and delivers neuromodulation pulses. The modulation controlcircuit 316 controls the delivery of the neuromodulation pulses usingthe plurality of modulation parameters. The combination of themodulation output circuit 315 and modulation control circuit 316 maycollectively be referred to as a pulse generator. The lead system 317includes one or more leads each configured to be electrically connectedto modulation device 312 and a plurality of electrodes 311-1 to 311-N(where N≥2) distributed in an electrode arrangement using the one ormore leads. Each lead may have an electrode array consisting of two ormore electrodes, which also may be referred to as contacts. Multipleleads may provide multiple electrode arrays to provide the electrodearrangement. Each electrode is a single electrically conductive contactproviding for an electrical interface between modulation output circuit315 and tissue of the patient. The neuromodulation pulses are eachdelivered from the modulation output circuit 315 through a set ofelectrodes selected from the electrodes 311-1 to 311-N. The number ofleads and the number of electrodes on each lead may depend on, forexample, the distribution of target(s) of the neuromodulation and theneed for controlling the distribution of electric field at each target.In one embodiment, by way of example and not limitation, the lead systemincludes two leads each having eight electrodes.

The neuromodulation system may be configured to modulate spinal targettissue or other neural tissue. The configuration of electrodes used todeliver electrical pulses to the targeted tissue constitutes anelectrode configuration, with the electrodes capable of beingselectively programmed to act as anodes (positive), cathodes (negative),or left off (zero). In other words, an electrode configurationrepresents the polarity being positive, negative, or zero. Otherparameters that may be controlled or varied include the amplitude, pulsewidth, and rate (or frequency) of the electrical pulses. Each electrodeconfiguration, along with the electrical pulse parameters, can bereferred to as a “modulation parameter set.” Each set of modulationparameters, including fractionalized current distribution to theelectrodes (as percentage cathodic current, percentage anodic current,or off), may be stored and combined into a modulation program that canthen be used to modulate multiple regions within the patient.

The number of electrodes available combined with the ability to generatea variety of complex electrical pulses, presents a huge selection ofmodulation parameter sets to the clinician or patient. For example, ifthe neuromodulation system to be programmed has sixteen electrodes,millions of modulation parameter sets may be available for programminginto the neuromodulation system. Furthermore, for example SCS systemsmay have thirty-two electrodes which exponentially increases the numberof modulation parameters sets available for programming. To facilitatesuch selection, the clinician generally programs the modulationparameters sets through a computerized programming system to allow theoptimum modulation parameters to be determined based on patient feedbackor other means and to subsequently program the desired modulationparameter sets.

Conventional programming for SCS therapy uses paresthesia to select anappropriate modulation parameter set. The paresthesia induced by themodulation and perceived by the patient should be located inapproximately the same place in the patient's body as the pain that isthe target of treatment. When leads are implanted within the patient, anoperating room (OR) mapping procedure may be performed to applyelectrical modulation to test placement of the leads and/or electrodes,thereby assuring that the leads and/or electrodes are implanted ineffective locations within the patient. According to variousembodiments, programming for sub-perception modulation may prime theneural tissue to provide faster response times to the sub-perceptionmodulation as part of an OR mapping procedure.

Once the leads are correctly positioned, a fitting procedure, which maybe referred to as a navigation session, may be performed to program theexternal control device, and if applicable the neuromodulation device,with a set of modulation parameters that best addresses the painfulsite. Thus, the navigation session may be used to pinpoint the volume ofactivation (VOA) or areas correlating to the pain. The procedure may beimplemented to target the tissue during implantation, or afterimplantation should the leads gradually or unexpectedly move that wouldotherwise relocate the modulation energy away from the target site. Byreprogramming the neuromodulation device (typically by independentlyvarying the modulation energy on the electrodes), the VOA can often bemoved back to the effective pain site without having to re-operate onthe patient in order to reposition the lead and its electrode array.According to various embodiments, a navigation session forsub-perception modulation may prime the neural tissue to provide fasterresponse times to the sub-perception modulation.

Although various embodiments described in this document prime neuraltissue to provide faster responses to sub-perception modulation in orderto perform faster OR mapping or navigation sessions, the present subjectmatter is not limited to such programming. By way of example and notlimitation, some embodiment may prime the neural tissue beforedelivering the sub-perception modulation therapy to the neural tissuesimply to reduce the wash-in time of the therapy. Thus, by way ofexample, a patient may obtain pain relief much quicker with the primedneural tissue than without the primed neural tissue.

FIG. 4 illustrates an embodiment of a programming device 413, such asmay be implemented as the programming device 213 in the neuromodulationsystem of FIG. 2. The programming device 413 includes a storage device418, a programming control circuit 419, and a GUI 414. The programmingcontrol circuit 419 generates the plurality of modulation parametersthat controls the delivery of the neuromodulation pulses according tothe pattern of the neuromodulation pulses. In various embodiments, theGUI 414 includes any type of presentation device, such as interactive ornon-interactive screens, and any type of user input devices that allowthe user to program the modulation parameters, such as touchscreen,keyboard, keypad, touchpad, trackball, joystick, and mouse. The storagedevice 418 may store, among other things, modulation parameters to beprogrammed into the modulation device. The programming device 413 maytransmit the plurality of modulation parameters to the modulationdevice. In some embodiments, the programming device 413 may transmitpower to the modulation device. The programming control circuit 419 maygenerate the plurality of modulation parameters. In various embodiments,the programming control circuit 419 may check values of the plurality ofmodulation parameters against safety rules to limit these values withinconstraints of the safety rules.

In various embodiments, circuits of neuromodulation, including itsvarious embodiments discussed in this document, may be implemented usinga combination of hardware, software and firmware. For example, thecircuit of GUI, modulation control circuit, and programming controlcircuit, including their various embodiments discussed in this document,may be implemented using an application-specific circuit constructed toperform one or more particular functions or a general-purpose circuitprogrammed to perform such function(s). Such a general-purpose circuitincludes, but is not limited to, a microprocessor or a portion thereof,a microcontroller or portions thereof, and a programmable logic circuitor a portion thereof.

FIG. 5 illustrates, by way of example, an implantable neuromodulationsystem and portions of an environment in which system may be used. Thesystem is illustrated for implantation near the spinal cord. However,neuromodulation system may be configured to modulate other neuraltargets such as may be useful for delivering other therapies. The system520 includes an implantable system 521, an external system 522, and atelemetry link 523 providing for wireless communication betweenimplantable system 521 and external system 522. The implantable systemis illustrated as being implanted in the patient's body. The implantablesystem 521 includes an implantable modulation device (also referred toas an implantable pulse generator, or IPG) 512, a lead system 517, andelectrodes 511. The lead system 517 includes one or more leads eachconfigured to be electrically connected to the modulation device 512 anda plurality of electrodes 511 distributed in the one or more leads. Invarious embodiments, the external system 402 includes one or moreexternal (non-implantable) devices each allowing a user (e.g. aclinician or other caregiver and/or the patient) to communicate with theimplantable system 521. In some embodiments, the external system 522includes a programming device intended for a clinician or othercaregiver to initialize and adjust settings for the implantable system521 and a remote control device intended for use by the patient. Forexample, the remote control device may allow the patient to turn atherapy on and off and/or adjust certain patient-programmable parametersof the plurality of modulation parameters.

The neuromodulation lead(s) of the lead system 517 may be placedadjacent, i.e., resting near, or upon the dura, adjacent to the spinalcord area to be stimulated. For example, the neuromodulation lead(s) maybe implanted along a longitudinal axis of the spinal cord of thepatient. Due to the lack of space near the location where theneuromodulation lead(s) exit the spinal column, the implantablemodulation device 512 may be implanted in a surgically-made pocketeither in the abdomen or above the buttocks, or may be implanted inother locations of the patient's body. The lead extension(s) may be usedto facilitate the implantation of the implantable modulation device 512away from the exit point of the neuromodulation lead(s).

FIG. 6 illustrates, by way of example, an embodiment of a SCS system,which also may be referred to as a Spinal Cord Modulation (SCM) system.The SCS system 624 may generally include a plurality (illustrated astwo) of implantable neuromodulation leads 625, an implantable pulsegenerator (IPG) 626, an external remote controller RC 627, a clinician'sprogrammer (CP) 628, and an external trial modulator (ETM) 629. The IPG626 may be physically connected via one or more percutaneous leadextensions 630 to the neuromodulation leads 625, which carry a pluralityof electrodes 631. As illustrated, the neuromodulation leads 625 may bepercutaneous leads with the electrodes arranged in-line along theneuromodulation leads. Any suitable number of neuromodulation leads canbe provided, including only one, as long as the number of electrodes isgreater than two (including the IPG case function as a case electrode)to allow for lateral steering of the current. Alternatively, a surgicalpaddle lead can be used in place of one or more of the percutaneousleads. The IPG 626 includes pulse generation circuitry, also referred toas a pulse generator, that delivers electrical modulation energy in theform of a pulsed electrical waveform (i.e., a temporal series ofelectrical pulses) to the electrodes in accordance with a set ofmodulation parameters.

The ETM 629 may also be physically connected via the percutaneous leadextensions 632 and external cable 633 to the neuromodulation leads 625.The ETM 629 may have similar pulse generation circuitry as the IPG 626to deliver electrical modulation energy to the electrodes accordancewith a set of modulation parameters. The ETM 629 is a non-implantabledevice that is used on a trial basis after the neuromodulation leads 625have been implanted and prior to implantation of the IPG 626, to testthe responsiveness of the modulation that is to be provided. Functionsdescribed herein with respect to the IPG 626 can likewise be performedwith respect to the ETM 629.

The RC 627 may be used to telemetrically control the ETM 629 via abi-directional RF communications link 634. The RC 627 may be used totelemetrically control the IPG 626 via a bi-directional RFcommunications link 635. Such control allows the IPG 626 to be turned onor off and to be programmed with different modulation parameter sets.The IPG 626 may also be operated to modify the programmed modulationparameters to actively control the characteristics of the electricalmodulation energy output by the IPG 626. A clinician may use the CP 628to program modulation parameters into the IPG 626 and ETM 629 in theoperating room and in follow-up sessions.

The CP 628 may indirectly communicate with the IPG 626 or ETM 629,through the RC 627, via an IR communications link 636 or other link. TheCP 628 may directly communicate with the IPG 626 or ETM 629 via an RFcommunications link or other link (not shown). The clinician detailedmodulation parameters provided by the CP 628 may also be used to programthe RC 627, so that the modulation parameters can be subsequentlymodified by operation of the RC 627 in a stand-alone mode (i.e., withoutthe assistance of the CP 628). Various devices may function as the CP628. Such devices may include portable devices such as a lap-toppersonal computer, mini-computer, personal digital assistant (PDA),tablets, phones, or a remote control (RC) with expanded functionality.Thus, the programming methodologies can be performed by executingsoftware instructions contained within the CP 628. Alternatively, suchprogramming methodologies can be performed using firmware or hardware.In any event, the CP 628 may actively control the characteristics of theelectrical modulation generated by the IPG 626 to allow the desiredparameters to be determined based on patient feedback or other feedbackand for subsequently programming the IPG 626 with the desired modulationparameters. To allow the user to perform these functions, the CP 628 mayinclude a user input device (e.g., a mouse and a keyboard), and aprogramming display screen housed in a case. In addition to, or in lieuof, the mouse, other directional programming devices may be used, suchas a trackball, touchpad, joystick, touch screens or directional keysincluded as part of the keys associated with the keyboard. An externaldevice (e.g. CP) may be programmed to provide display screen(s) thatallow the clinician to, among other functions, to select or enterpatient profile information (e.g., name, birth date, patientidentification, physician, diagnosis, and address), enter procedureinformation (e.g., programming/follow-up, implant trial system, implantIPG, implant IPG and lead(s), replace IPG, replace IPG and leads,replace or revise leads, explant, etc.), generate a pain map of thepatient, define the configuration and orientation of the leads, initiateand control the electrical modulation energy output by theneuromodulation leads, and select and program the IPG with modulationparameters in both a surgical setting and a clinical setting.

An external charger 637 may be a portable device used totranscutaneously charge the IPG via a wireless link such as an inductivelink 638. Once the IPG has been programmed, and its power source hasbeen charged by the external charger or otherwise replenished, the IPGmay function as programmed without the RC or CP being present.

FIG. 7 illustrates, by way of example, some features of theneuromodulation leads 725 and a pulse generator 726. The pulse generator726 may be an implantable device (IPG) or may be an external device suchas may be used to test the electrodes during an implantation procedure.In the illustrated example, one of the neuromodulation leads has eightelectrodes (labeled E1-E8), and the other neuromodulation lead has eightelectrodes (labeled E9-E16). The actual number and shape of leads andelectrodes may vary for the intended application. An implantable pulsegenerator (IPG) may include an outer case for housing the electronic andother components. The outer case may be composed of an electricallyconductive, biocompatible material, such as titanium, that forms ahermetically-sealed compartment wherein the internal electronics areprotected from the body tissue and fluids. In some cases, the outer casemay serve as an electrode (e.g. case electrode). The IPG may includeelectronic components, such as a controller/processor (e.g., amicrocontroller), memory, a battery, telemetry circuitry, monitoringcircuitry, modulation output circuitry, and other suitable componentsknown to those skilled in the art. The microcontroller executes asuitable program stored in memory, for directing and controlling theneuromodulation performed by IPG.

Electrical modulation energy is provided to the electrodes in accordancewith a set of modulation parameters programmed into the pulse generator.The electrical modulation energy may be in the form of a pulsedelectrical waveform. Such modulation parameters may comprise electrodecombinations, which define the electrodes that are activated as anodes(positive), cathodes (negative), and turned off (zero), percentage ofmodulation energy assigned to each electrode (fractionalized electrodeconfigurations), and electrical pulse parameters, which define the pulseamplitude (measured in milliamps or volts depending on whether the pulsegenerator supplies constant current or constant voltage to the electrodearray), pulse width (measured in microseconds), pulse rate (measured inpulses per second), and burst rate (measured as the modulation onduration X and modulation off duration Y). The electrical pulseparameters may define an intermittent modulation with “on” periods oftime where a train of two or more pulses are delivered and “off” periodsof time where pulses are not delivered. Electrodes that are selected totransmit or receive electrical energy are referred to herein as“activated,” while electrodes that are not selected to transmit orreceive electrical energy are referred to herein as “non-activated.”

Electrical modulation occurs between or among a plurality of activatedelectrodes, one of which may be the IPG case. The system may be capableof transmitting modulation energy to the tissue in a monopolar ormultipolar (e.g., bipolar, tripolar, etc.) fashion. Monopolar modulationoccurs when a selected one of the lead electrodes is activated alongwith the case of the IPG, so that modulation energy is transmittedbetween the selected electrode and case.

Any of the electrodes E1-E16 and the case electrode may be assigned toup to k possible groups or timing “channels.” In one embodiment, k mayequal four. The timing channel identifies which electrodes are selectedto synchronously source or sink current to create an electric field inthe tissue to be stimulated. Amplitudes and polarities of electrodes ona channel may vary. In particular, the electrodes can be selected to bepositive (anode, sourcing current), negative (cathode, sinking current),or off (no current) polarity in any of the k timing channels. The IPGmay be operated in a mode to deliver electrical modulation energy thatis therapeutically effective and causes the patient to perceive deliveryof the energy (e.g. therapeutically effective to relieve pain withperceived paresthesia), and may be operated in a sub-perception mode todeliver electrical modulation energy that is therapeutically effectiveand does not cause the patient to perceive delivery of the energy (e.g.therapeutically effective to relieve pain without perceivedparesthesia). Some embodiments may use one channel to prime the neuraltissue with a sub-perception modulation field, and use another channelto deliver therapeutic sub-perception modulation to the neural tissue.

The IPG may be configured to individually control the magnitude ofelectrical current flowing through each of the electrodes. For example,a current generator may be configured to selectively generate individualcurrent-regulated amplitudes from independent current sources for eachelectrode. In some embodiments, the pulse generator may have voltageregulated outputs. While individually programmable electrode amplitudesare desirable to achieve fine control, a single output source switchedacross electrodes may also be used, although with less fine control inprogramming. Neuromodulators may be designed with mixed current andvoltage regulated devices.

FIG. 8 is a schematic view of a single electrical modulation lead 839implanted over approximately the longitudinal midline of the patient'sspinal cord 840. FIG. 9 illustrates an embodiment where an electricalmodulation lead 941 has been implanted more laterally with respect tothe spinal cord, thereby placing it proximate the dorsal horn of thespinal cord, and the other electrical modulation lead 942 has beenimplanted more medially with respect to the spinal cord, thereby placingit proximate the dorsal column of the spinal cord 940.

It is understood that additional leads or lead paddle(s) may be used,such as may be used to provide a wider electrode arrangement and/or toprovide the electrodes closer to dorsal horn elements, and that theseelectrode arrays also may implement fractionalized current.

Placement of the lead more proximate to the DH than the DC may bedesirable to preferentially stimulate DH elements over DC neuralelements for a sub-perception therapy. Lead placement may also enablepreferential modulation of dorsal roots over other neural elements. Anyother plurality of leads or a multiple column paddle lead can also beused. Longitudinal component of the electrical field is directed alongthe y-axis depicted in FIG. 8, and a transverse component of theelectrical field is directed along the x-axis depicted in FIG. 8.

FIG. 10 is a schematic view of the electrical modulation lead 1043showing an example of the fractionalization of the anodic currentdelivered to the electrodes on the electrical modulation lead. Thesefigures illustrate fractionalization using monopolar modulation where acase electrode of the IPG is the only cathode, and carries 100% of thecathodic current. The fractionalization of the anodic current shown inFIG. 10 does not deliver an equal amount of current to each electrode1044, because this embodiment takes into account electrode/tissuecoupling differences, which are the differences in how the tissueunderlying each electrode reacts to electrical modulation. Also, theends of the portion of the electrical modulation lead include electrodeshaving lower gradient in the longitudinal direction. The magnitude ofthe electrical field tapers down at the ends of the electricalmodulation lead. Fractionalization of the current may accommodatevariation in the tissue underlying those electrodes. Thefractionalization across the electrical modulation lead can vary in anymanner as long as the total of fractionalized currents equals 100%.Various embodiments described herein implement a programmed algorithm todetermine the appropriate fractionalization to achieve a desiredmodulation field property.

Modulation thresholds vary from patient to patient and from electrode toelectrode within a patient. An electrode/tissue coupling calibration ofthe electrodes may be performed to account for these differentmodulation thresholds and provide a more accurate fractionalization ofthe current between electrodes. For example, perception threshold may beused to normalize the electrodes. The RC or the CP may be configured toprompt the patient to actuate a control element, once paresthesia isperceived by the patient. In response to this user input, the RC or theCP may be configured to respond to this user input by storing themodulation signal strength of the electrical pulse train delivered whenthe control element is actuated. Other sensed parameter orpatient-perceived modulation values (e.g. constant paresthesia, ormaximum tolerable paresthesia) may be used to provide theelectrode/tissue coupling calibration of the electrodes.

The SCS system may be configured to deliver different electrical fieldsto achieve a temporal summation of modulation. The electrical fields canbe generated respectively on a pulse-by-pulse basis. For example, afirst electrical field can be generated by the electrodes (using a firstcurrent fractionalization) during a first electrical pulse of the pulsedwaveform, a second different electrical field can be generated by theelectrodes (using a second different current fractionalization) during asecond electrical pulse of the pulsed waveform, a third differentelectrical field can be generated by the electrodes (using a thirddifferent current fractionalization) during a third electrical pulse ofthe pulsed waveform, a fourth different electrical field can begenerated by the electrodes (using a fourth different currentfractionalized) during a fourth electrical pulse of the pulsed waveform,and so forth, These electrical fields may be rotated or cycled throughmultiple times under a timing scheme, where each field is implementedusing a timing channel. The electrical fields may be generated at acontinuous pulse rate, or may be bursted on and off. Furthermore, theinterpulse interval (i.e., the time between adjacent pulses), pulseamplitude, and pulse duration during the electrical field cycles may beuniform or may vary within the electrical field cycle.

Some embodiments are configured to determine a modulation parameter setto create a field shape to provide a broad and uniform modulation fieldsuch as may be useful to prime targeted neural tissue withsub-perception modulation. Some embodiments are configured to determinea modulation parameter set to create a field shape to reduce or minimizemodulation of non-targeted tissue (e.g. DC tissue). Various embodimentsdisclosed herein are directed to shaping the modulation field to enhancemodulation of some neural structures and diminish modulation at otherneural structures. The modulation field may be shaped by using multipleindependent current control (MICC) or multiple independent voltagecontrol to guide the estimate of current fractionalization amongmultiple electrodes and estimate a total amplitude that provide adesired strength. For example, the modulation field may be shaped toenhance the modulation of DH neural tissue and to minimize themodulation of DC tissue. A benefit of MICC is that MICC accounts forvarious in electrode-tissue coupling efficiency and perception thresholdat each individual contact, so that “hot-spot” stimulation iseliminated.

Sub-perception SCS typically does not provide a quick feedback responseregarding the effectiveness of the therapy. Rather, it has been observedthat a wash-in period (a period of time for a delivered therapy to betherapeutically effective) for the sub-perception SCS is typically aboutone day. Thus, when the programmed modulation parameters are changed tochange the location of the sub-perception modulation field, the patientmay not be able to determine the effect that the changes have (e.g. painrelief) for a day or so. This make it difficult quickly titrate themodulation field of the sub-perception SCS to provide effective painrelief to the patient.

It has been observed during research that priming the neural tissueenables faster pain relief feedback from the patient during the searchfor the modulation field sweet spot. It may be appropriate to considerthat priming the neural tissue “warms up” the neural tissue in a mannerthat reduces the wash-in time. However, neural physiology is complex andit is not currently understood why the primed neural tissue reduces thewash-in time of the sub-perception therapy such that the patient canquickly feel pain relief. It is noted that “priming” is different thanconditioning pre-pulses which are delivered immediately before theneuromodulation pulse. A conditioning pre-pulse is timed to make a nervemore susceptible or less susceptible to capture by the immediatelysubsequent neuromodulation pulse. Thus, a conditioning pre-pulse as aspecific relationship to a neuromodulation pulse. In contrast, the primemodulation field extends over a much longer period of time. Further,rather than making neural tissue more or less excitable by a pulse, theprime modulation field reduces a wash-in time of a therapy to make apatient feel the effects of the therapy (e.g. pain relief) much morequickly than would be felt without the prime field.

Various embodiments may deliver a low intensity, modulation field inpreparation to test for and find the sweet-spot for the modulationfield. The preparatory, lower intensity field is referred to herein as aprime field, as it is used to prime the neural tissue to be tested tohave a quicker response to during the testing for the modulation sweetspot for pain relief. The prime field can be a supra-perception orsub-perception modulation field, but is typically even lower than thetherapeutic sub-perception modulation field.

A test region of neural tissue represents a region of tissue that is tobe tested for a sweet spot. The test region may include many potentiallocations for targeting the modulation field. The test region may spanalong the entire electrode arrangement (e.g. lead(s)) or may be reducedto a portion of the electrode arrangement. Priming may also be appliedin a trolling fashion to cover the entire test region. As it is notknown what location is to be most effective, the entire test region isprimed.

In a non-limiting example to illustrate the lower intensity of the primemodulation field, one may assume that a patient may feel paresthesia orotherwise perceive the delivery of the modulation field when themodulation current has an amplitude of 10 mA. Thus, 10 mA may beconsidered to be a perception threshold for the modulation. Therapeuticsub-perception modulation maybe delivered within a range of 30% to 90%of the perception threshold. Thus, in this example, modulation with anamplitude between 3 mA and 9 mA may be therapeutically effective (e.g.provide pain relief). Priming the neural tissue may be accomplishedusing amplitudes near the lower range of the sub-perception modulationor even below the lower range of the sub-perception modulation such as,by way of example, between 2 mA to 4 mA. The sub-perception modulationaffects the neural tissue, but not to the point where the modulationinduces the nerve to trigger action potentials. Thus, the prime fieldmay affect the ion concentrations within and outside of the neuralpathways responsible for pain relief and/or may affect neurotransmittersresponsible for pain relief, such that additional changes bysub-perception modulation may more quickly induce desirable actionpotentials in these neural pathways responsible for pain relief.

FIGS. 11A-11B illustrate, by way of example and not limitation,electrode arrangements (e.g. E1-E8 in FIG. 11A and E1-E16 in FIG. 11B)and test regions 1145 of neural tissue along the electrode arrangements.These test regions 1145 may extend across the entire electrodearrangement. In some embodiments, the test regions may extend along onlya portion of the electrode arrangement. By way of example, someembodiments may allow a user to select the test region and thus selectthe portion of the electrode arrangement to be tested. In the exampleillustrated in FIG. 11A the test region is neural tissue along the E2 toE7 electrodes, and in the example illustrated in FIG. 11B the testregion is neural tissue along the E2 through E7 and the E10 to E15electrodes.

The electrodes in the electrode arrangement may be fractionalized, usingdifferent modulation parameter sets, to change the portion of the neuraltissue that is modulated. Thus, there may be many neural tissuelocations that can be targeted with the test region of neural tissueadjacent to the electrode arrangement. FIGS. 12A-12C illustrate, by wayof example and not limitation, neural tissue locations 1246 that may betargeted within the test region in one, two and three dimensions,respectively. In the one-dimensional example illustrated in FIG. 12A,the neural locations that may be targeted may simply be a line ofpotential targets such as may be observed from a single lead with alinear arrangement of electrodes. In the two dimensional exampleillustrated in FIG. 12B the neural locations that may be targeted may beconsidered to lie in a plane proximate to the electrode arrangement. Inthe three-dimensional example illustrated in FIG. 12C, the neurallocations that may be targeted may be considered to be a volume oftissue proximate to the electrode arrangement. By way of example, thetwo-dimensional and three-dimensional test regions may be implementedusing two or more leads of electrodes. Thus, the test regions may berelatively simple or complex shapes, and may include relatively few orrelatively many locations to be tested.

FIG. 13 illustrates an example of a method for finding a sweet spot forsub-perception modulation. In the illustrated example, a test region isprimed with the sub-perception modulation field 1347, and the sweet-spottest is performed 1348 to find location of neural tissue that istherapeutically effective when targeted with sub-perception modulation.The sweet spot test may involve a manual process to reprogram themodulation field parameter set with different values to change thetargeted location of the modulation field. In some embodiments of thetest, the targeted location is automatically changed (e.g. trolled) byautomatically changing values of the modulation field parameter set.Some embodiments may semi-automatically change values of the modulationfield parameter set to change the targeted location of the modulationfield.

At 1349, a first location in the test region is tested by focusing themodulation field onto the first location. At 1350, the therapeuticeffect of modulating the first location is assessed. In an example wherethe therapy is a therapy to alleviate pain, the patient may provide thisassessment by quantifying a level of pain or level of pain relief thatthey are experiencing. In some examples, a biomarker is used to providean assessment of the therapeutic efficacy of the modulation fieldfocused on the tested location. At 1351, the modulation field parameterset is changed to change the focus of the modulation field to test asecond location in the test region. At 1352, the therapeutic effect ofmodulating the second location is assessed. If more location(s) are tobe tested, as illustrated at 1353, the process may continue to 1354 totest the next location and to 1355 to assess the therapeutic effect ofthe next location. The process may determine or identify the location(s)that are therapeutically effective 1356 by evaluating the quantifiedeffects of the therapy. In some embodiments, the quantified effects maybe compared to each other to identify the tested location that has thebest therapeutic effect (the sweet spot) or one of the best therapeuticeffects (a sweet spot).

The present subject matter may be used to test relatively smalllocations using a more narrowly focused modulation field such asgenerally illustrated above in FIGS. 12A-12C, or may be used to testrelatively larger locations of neural tissue using a more uniform (lessfocused) modulation field. The test of larger locations may be followedby a more focused test or tests within one of the larger location.Regardless of whether the test location is relatively large orrelatively small, the present subject matter primes the test neuraltissue to reduce a wash-in time of the therapy and enable a quickassessment of the effectiveness of the therapy. A few search algorithmsare provided below as examples. Other processes for testing locations ofneural tissue are possible.

Various embodiments start with full-lead then use a search algorithm toreduce the span and improve energy efficiency. This can be done from theRC or CP, or in the IPG with RC feedback. The proposed algorithms mayrely on some form of feedback indicating the effectiveness of themodulation. For example, a patient may provide feedback regarding painrelief. Feedback may also provide a biomarker signal.

The system may include a routine to confirm that the modulation alongthe full lead is effective and then focus the modulation along a portionof the lead. Thus, for example, a generally uniform modulation field maybe provided along this smaller portion of the lead. This field is stillbroad as it may be provided across an area with multiple electrodecontacts, but it is less than the entire electrode arrangement usingelectrode array(s) on the lead(s).

Various embodiments may provide a rostra-caudal focus routine thatincludes a binary search routine. The binary search routine segments thelead or array of electrodes from a full set of electrodes into at leasttwo subsets of electrodes that defines partial lead search regions. Thebinary search routine may confirm that modulation along the full lead iseffective.

FIG. 14 illustrates, by way of example, aspects of a binary searchroutine as a rostra-caudal focus routine. A first subset of electrodesthat define a first partial lead search region can be tested todetermine if the modulation is effective using the first subset 1457. Ifit is effective, the first subset of electrodes that define the firstpartial lead search region may be used to deliver the modulation 1458 orfor further more focused tests. If it is not effective, then a secondsubset of electrodes that define a second partial lead search region maybe tested to determine if the second subset of electrodes is effective1459. If it is effective, the second subset of electrodes that definethe second partial lead search region may be used to deliver themodulation 1458. If it is not effective, then a third (or nth) subset ofelectrodes that define a third (or nth) partial lead search region maybe tested to determine if the third (or nth) subset of electrodes iseffective 1460. If it is effective, the third (or nth) subset ofelectrodes that define the third (or nth) partial lead search region maybe used to deliver the modulation 1458. If it is not effective, then thebinary search process may return to the full list of electrodes 1461which was previously determined to be effective. At least some of thesubsets of electrodes may be exclusive of each other. At least some ofthe subsets of electrodes may intersect with each other. In someembodiments, at least two subsets are exclusive, and at least one subsethas an intersection with another subset.

FIG. 15 illustrates an example of the binary search routine. The leadhas a full span 1562 which may be split into three partial lead searchregions 1563, 1564 and 1565, each partial search region including acorresponding subset of electrodes. By way of example and notlimitation, the first and second subsets 1563 and 1564 of electrodes maybe mutually exclusive, and third subset 1565 may include an intersectionwith the first subset and also may include an intersection with thesecond set. In an example, the full lead may be bifurcated to providethe first partial lead search region 1563 on a first side of the lead(e.g. left end of electrode array to middle) and the second partial leadsearch region 1564 on a second side of the lead (e.g. right end of theelectrode array to middle). The third partial lead search region 1565may partially overlap each of the first and second partial lead searchregions. Thus, the partial lead search regions may define a first endregion, a second end region and a middle region of the lead.

FIGS. 16A-16C illustrate, by way of example, an edge search routine. Theedge search routine progressively moves each edge of the activeelectrodes in the array toward the middle and confirms that themodulation remains effective with the moves. Thus, a first edge can bemoved toward the center until the next move toward the center causes themodulation to be ineffective; and a second edge can be moved toward thecenter until the next move toward the center causes the modulation to beineffective.

For example, the edge search routine may include selecting an edge ofthe electrode arrangement (e.g. array) for movement 1666. The selectededge may be one of the two edges 1667A or 1667B illustrated in FIG. 16B.However, there can be more than two edges if more than two regions arebeing focused. The selected edge is moved inward 1668 toward the otheredge for the region of interest. If the reduced set of electrodes is nolonger therapeutically effective 1669, then the previous move can beundone and that edge can be set so that is no longer is capable of beingselected for movement 1670. The process can return to 1666 to attempt tomove the other edge(s). If the reduced set of electrodes continues to betherapeutically effective 1669, then the process returns to 1666 tocontinue moving edges until such time as all of the edges are set 1671.The final reduced set 1672 of electrodes can be used 1673 to deliver themodulation energy.

According to various embodiments, the programmed system may beconfigured with a neuromodulation focus routine such as a rostra-caudalfocus routine to allow a user to select the desired electrodes for theneuromodulation to be more specific to the desired physiological area.Some embodiments may allow non-contiguous spans to be selected as aresult of initial programming and/or neuromodulation refinement lateron.

The modulation field may be moved from location to location using anautomatic trolling process or through patient control. Candidatetrolling algorithms include a monopolar troll (anodic or cathodic) or abipolar troll or a multipolar troll. The troll can be done with MICC ormultiple independent voltage control, or with a timing channelinterleaving technique. MICC enables the locus of the modulation to begradually moved across along the lead or within the array of electrodes.The interleaving of timing channels allows different electrode(s) indifferent timing channels. Values of stimulation parameter(s) (e.g.amplitude) in the timing channels can be adjusted. Thus by way ofexample and not limitation, if a monopolar modulation is delivered usinga first electrode in a first channel and another monopolar modulation isdelivered using a second electrode adjacent to the first electrode in asecond channel, then the amplitude of the monopolar modulation in thefirst channel may be incrementally reduced as the amplitude of themonopolar modulation may be increase in the second channel. In thismatter, the locus of the modulation may be gradually adjusted.

Various embodiments troll a modulation field, using an arrangement ofelectrodes on at least one lead, through neural tissue positions, andperform a quantification procedure multiple times as the modulationfield is trolled through the positions. The quantification procedureidentifies when the modulation field provides a therapeutic effect (e.g.pain relief). The quantification procedure may include receiving amarking signal that indicates that a modulation intensity achieved thetherapeutic effect, and storing a value for the therapeutic effect aswell as modulation field parameter data. The modulation intensity mayinclude modulation parameters that affect the patient's perception ofthe modulation energy. These parameters may include pulse width, rate,amplitude, distribution of current, and electrode polarity (cathode v.anode). By way of example and not limitation, the storage of theparameter data may be in a temporary storage such as but not limited tocache or RAM or in permanent/persistent storage such as but not limitedto ROM, a memory device such a hard drive, optical disc, thumb drive, orcloud storage. The quantification process may include receiving atitration signal that indicates an instruction to adjust modulationintensity, and adjusting the modulation intensity in response toreceiving the titration signal. The titration signal may be initiated bya patient, or by a clinician or other user who is responding to patientresponses.

FIG. 17 illustrates an example of a system for finding a sweet-spot forsub-perception modulation. The system may include an electrodearrangement 1711, a modulation device 1712, and an external device suchas a programmer or remote control (RC) 1713. The illustrated electrodearrangement 1711 includes electrodes corresponding to a test region 1774of neural tissue, The test region is proximate to the electrodes, andmay be associated with all electrodes in the electrode arrangement or asubset of the electrodes in the electrode arrangement. The test region1774 may include targeted location(s) 1775 which may be, as discussedabove, a relatively focused small location or a relatively broadlocation.

The modulation device 1712 may include a neural modulator generator 1776which may comprise a modulation output circuit and a modulation controlcircuit such as is generally illustrated in FIG. 3. The modulationdevice may further include memory 1777, which may include modulationfield parameter sets 1778 and a sweet spot test routine 1779. Themodulation field parameter sets may be used by the neuromodulatorgenerator to control the modulation field generated by the electrodearrangement. The modulation field parameter sets may include a firstsub-perception modulation field parameter set used by the neuromodulatorgenerator to prime a test region, and include a second sub-perceptionmodulation field parameter set used by the neuromodulator to testlocation(s) within the test region. The sweet spot test routine 1779 mayinclude instructions for targeting location(s) within the test regions.The instructions for targeting location(s) may include instructions forreceiving manual control inputs from a user or may include instructionsfor performing automated or semi-automated trolling of the movements.The sweet spot test routine 1779 may also include instructions forreceiving feedback concerning the effective of the therapy. For example,the instructions may include instructions for receiving a quantificationof the therapeutic effect (e.g. a pain rating) from the external device,and associating that quantification with the targeted location.

The external device 1713 may include a graphical user interface (GUI)1780. Some embodiments of the GUI may provide test region selectionelement(s) 1781 used to select a test region. Some embodiments may alsodisplay the selected test region with respect to the electrodearrangement. Some embodiments of the GUI may include prime modulationelement(s) 1782 used to program the first sub-perception modulationfield parameter set that controls location and shape of the primemodulation field, and test element(s) 1783 used to program the secondsub-perception modulation filed parameter set that controls location andshape of the second modulation field used in performing the sweet spottest. Some embodiments of the GUI may include an intensity controlelement(s) 1784 configured for use by the user to control the intensityof the first and/or second sub-perception modulation fields. Theintensity of the stimulation maybe controlled by controlling anamplitude of the modulation pulses. In addition or as an alternative,the intensity of the stimulation may be controlled by controlling apulse with of the modulation pulses, the pulse burst duration, the dutycycle of the pulses, the burst on/burst off duty cycle and/or pulsefrequency of the modulation pulses. Some GUI embodiments provide anelement to provide an indicator 1785 of a graphical lead with a testregion identified in relative position with respect to the illustratedlead. Some embodiments may allow the user to set or adjust the testregion, such as by dragging illustrated boundaries of the test region onthe GUI. Some GUI embodiments provide an element 1786 to provide anindicator of targeted location(s) within a test region, and someembodiments may allow the user to set or adjust the targetedlocation(s). A GUI example may include element(s) 1787 to allow a userto enter feedback regarding the effective of the therapy. For example,the feedback may be a quantification of pain or pain relief.

FIG. 18 illustrates, by way of example, and not limitation,sub-perception modulation intensity used to prime the test region and totest a therapeutic effect of locations within the test region. Theperception threshold 1888 illustrates the intensity of the modulationfield at the boundary between perceptible modulation and sub-perceptionmodulation. Perceptible modulation is where the modulation fielddelivers energy that is perceptible to the patient. Examples ofperceptible stimulation include stimulation that causes paresthesia.Perceptible modulation may also include modulation that causes atemperature change or a motor response. The therapeutic sub-perceptionmodulation 1889 is therapeutically effective, even though the deliveryof the modulation energy is not perceived by the patient. As discussedearlier, the perception threshold may be different for differentportions of the electrode arrangement. Some embodiments calibrate themodulation to account for these differences. The prime sub-perceptionmodulation 1890 is generally at a lower energy than the sub-perceptionmodulation 1889.

FIGS. 19A-19B illustrate relative timing between the prime modulationfield 1991 and the sweet spot test session 1992 to test a therapeuticeffect of locations within the test region. In both examples, the primemodulation field 1991 is delivered for a time period 1993 before thesweet spot test session 1992. For example, this time period 1993 may bemore than 30 minutes. In some embodiments, this time period 1993 is morethan an hour. In some embodiments the time period 1993 is more than 6hours and less than a week. In some embodiments, the time period 1993 islonger than 1 day and shorter than 3 days. In the embodiment illustratedin FIG. 19A, the prime modulation field 1991 is stopped before the sweetspot test session 1992 begins. There may be a time period 1994 betweenthe prime modulation field and the sweet spot test session without anymodulation. In some embodiments, the prime-modulation field continuesduring at least a portion of the sweet spot test session. FIG. 19Billustrates an example in which the sweet spot test session 1992 isperformed while the prime modulation field 1991 is generated. The sweetspot test session may be performed during an operation room mappingsession and/or during a navigation fitting session.

In addition to the Examples discussed in the Summary Section above, someother non-limiting examples are provided as follows.

An example (e.g., “Example 26”) of a system includes an electrodearrangement, a neuromodulation generator, a memory, and a controller.The neuromodulation generator may be configured to use electrodes in theelectrode arrangement to generate modulation fields. The modulationfields may include a first sub-perception modulation field over a testregion of neural tissue along the electrode arrangement to prime theneural tissue throughout the test region and a second sub-perceptionmodulation field to test a plurality of targeted locations of neuraltissue within the test region for therapeutic effectiveness. The memorymay be configured to store a first modulation field parameter set foruse to generate the first sub-perception modulation field, and a secondmodulation field parameter set for use to generate the secondsub-perception modulation field to modulate one targeted region of theplurality of the targeted locations within the test region. The secondmodulation field parameter set may be programmable to change the secondsub-perception modulation field to modulate other ones of the pluralityof targeted locations. The controller may be configured to control theneuromodulation generator to use the first modulation field parameterset to prime the test region with the first sub-perception modulationfield and to use the second modulation field parameter set to deliver asecond sub-perception modulation field to modulate the one of thetargeted locations within the test region.

In Example 27, the subject matter of Example 26 may optionally beconfigured such that the controller is configured to generate the firstsub-perception modulation field to prime the test region for a period oftime before the second sub-perception modulation field.

In Example 28, the subject matter of Example 27 may optionally beconfigured such that the period of time is over 30 minutes.

In Example 29, the subject matter of Example 28 may optionally beconfigured such that the period of time is between one hour and oneweek.

In Example 30, the subject matter of any one or any combination ofExamples 27-29 may optionally be configured such that the controller isconfigured to stop generating the first sub-perception modulation fieldbefore generating the second sub-perception modulation field.

In Example 31, the subject matter of any one or any combination ofExamples 27-29 may optionally be configured such that the controller isconfigured to generate the first sub-perception modulation field for atleast a portion of a time when the second sub-perception modulationfield is generated.

In Example 32, the subject matter of any one or any combination ofExamples 26-31 may optionally be configured such that the controller isconfigured to implement a trolling routine to troll the secondsub-perception modulation field through the plurality of targetedlocations within the test region of neural tissue.

In Example 33, the subject matter of Example 32 may optionally beconfigured such that the trolling routine implemented by the controlleris configured to perform at least one of automatically moving the secondsub-perception modulation field or receiving a user-controlled trollingcommand to control movement of the second sub-perception modulationfield.

In Example 34, the subject matter of Example 33 may optionally beconfigured such that the programmable second modulation field parameterset includes programmable fractionalized current values for electrodeswithin the electrode arrangement, and modification of the programmablefractionalized current values moves the second sub-perception modulationfield.

In Example 35, the subject matter of any one or any combination ofExamples 32-34 may optionally be configured such that the controller isconfigured to implement a routine as the second sub-perceptionmodulation field is trolled through the plurality of targeted positionswithin the test region to identify a therapeutically-effective locationin the test region where the second sub-perception modulation fieldprovides pain relief, and to store in the memory the modulation fieldparameter data that provides the pain relief as the second modulationfield parameter set.

In Example 36, the subject matter of Example 35 may optionally beconfigured such that the therapeutically-effective location is a testedlocation within the test region of neural tissue that is most effectivein providing pain relief.

In Example 37, the subject matter of any one or any combination ofExamples 35-36 may optionally be configured such that the routineimplemented by the controller is configured to receive a titrationsignal that indicates an instruction to adjust an intensity of thesecond sub-perception modulation field, adjust the intensity in responseto receiving the titration signal, and receive an indication signal thatthe adjusted modulation intensity achieved the pain relief.

In Example 38, the subject matter of Example 37 may optionally beconfigured such that the titration signal includes anautomatically-provided signal to automatically adjust the intensity ofthe second sub-perception modulation field. The system may be configuredto receive a user-provided command to stop the automatic adjustment ofthe intensity of the second sub-perception modulation field.

In Example 39, the subject matter of any one or any combination ofExamples 26-38 may optionally be configured such that the controller isconfigured to use a timing channel to prime the test region and to useat least one other timing channel to generate to deliver the therapeuticsub-perception modulation.

In Example 40, the subject matter of any one or any combination ofExamples 26-39 may optionally be configured such that the systemincludes an implantable device and an external device. The implantabledevice includes the neuromodulation generator, the memory and thecontroller. The external device and the implantable device areconfigured to communicate. The external device is configured to providea graphical user interface to provide at least one of: a graphical leadindicator configured to indicate the test region of neural tissue and atleast one targeted region of the plurality of the targeted locationswithin the test region.

An example of a method (e.g., “Example 41”) is also provided. The methodmay include generating a first sub-perception modulation field over atest region of neural tissue along an electrode arrangement to prime theneural tissue throughout the test region, and generating a secondmodulation field to test a plurality of targeted locations of neuraltissue within the test region for therapeutic effectiveness,

In Example 42, the subject matter of generating the first sub-perceptionmodulation field as found in Example 41 may optionally includegenerating the first sub-perception modulation field over the testregion of neural tissue along the electrode arrangement to prime theneural tissue throughout the test region for a period of time beforegenerating the second sub-perception modulation field.

In Example 43, the subject matter of the period of time as found inExample 42 may optionally include that the period of time is over 30minutes.

In Example 44, the subject matter of any one or any combination ofExamples 42-43 may optionally further include stopping the firstsub-perception modulation field before generating the secondsub-perception modulation field.

In Example 45, the subject matter of generating the first sub-perceptionmodulation field as found in any one or any combination of Examples42-43 may optionally include generating the first sub-perceptionmodulation field for at least a portion of a time when the secondsub-perception modulation field is generated.

In Example 46, the subject matter of any one or any combination ofExamples 41-45 may optionally further include trolling the secondsub-perception modulation field through the plurality of targetedlocations within the test region of neural tissue. The trolling includesautomatically moving the second sub-perception modulation field, orreceiving a user-controlled trolling command to control movement of thesecond sub-perception modulation field.

In Example 47, the subject matter of generating the secondsub-perception modulation field as found in any one or any combinationof Examples 41-46 may optionally include using a programmable secondmodulation field parameter set to generate the second sub-perceptionmodulation field to modulate one of the plurality of the targetedlocations within the test region.

In Example 48, the subject matter of Example 47 may optionally furtherinclude programming different values for the programmable secondmodulation field parameter set to move the second sub-perceptionmodulation field to different ones of the plurality of targetedlocations within the test region of neural tissue.

In Example 49, the subject matter of any one or any combination ofExamples 41-48 may optionally further include implementing a routine toidentify a therapeutically-effective location in the test region wherethe modulation field provides pain relief, and programming themodulation field parameter data that provides the pain relief as thesecond modulation field parameter set.

In Example 50, the subject matter of implementing the routine toidentify the therapeutically-effective location as found in Example 49may optionally include identifying a tested location within the testregion of neural tissue that is most effective in providing pain relief.

The above detailed description is intended to be illustrative, and notrestrictive. The scope of the disclosure should, therefore, bedetermined with references to the appended claims, along with the fillscope of equivalents to which such claims are entitled.

What is claimed is:
 1. A method for delivering neuromodulation,comprising: generating a first modulation field over a region of neuraltissue using electrodes and first fractionalized current values for theelectrodes; generating a second modulation field using the electrodesand second fractionalized current values for the electrodes; andadjusting the second fractionalized current values to focus the secondmodulation field on each location of a plurality of locations within theregion of neural tissue.
 2. The method of claim 1, wherein the firstmodulation field and the second modulation field each comprise asub-perception modulation field.
 3. The method of claim 1, wherein atleast one of the first modulation field or the second modulation fieldcomprises a supra-perception modulation field.
 4. The method of claim 3,wherein the first modulation field is a supra-perception field, and thesecond modulation field is a sub-perception field.
 5. The method ofclaim 1, wherein the first modulation field is applied in a trollingfashion to cover the region of neural tissue.
 6. The method of claim 1,wherein the plurality comprises: a plurality of large locations; and aplurality of small locations within each large location of the pluralityof large locations, and adjusting the second fractionalized currentvalues to focus the second modulation field on each location of theplurality of locations comprises: adjusting the second fractionalizedcurrent values to focus the second modulation field on each largelocation of the plurality of large locations; and adjusting the secondfractionalized current values to focus the second modulation field oneach second locations of the plurality of small locations within theeach large location.
 7. The method of claim 1, further comprisinggenerating the first modulation field over the region of neural tissuefor a period of time before generating the second modulation field. 8.The method of claim 1, further comprising generating the firstmodulation field over the region of neural tissue for a first period oftime and generating the second modulation field for a second period oftime, wherein the first period of time and the second period of time atleast partially overlap.
 9. A system for delivering neuromodulation,comprising: electrodes; a neuromodulation generator configured to:generate a first modulation field over a region of neural tissue usingthe electrodes and first fractionalized current values for theelectrodes; and generate a second modulation field using the electrodesand second fractionalized current values for the electrodes, and acontroller configured to control the first fractionalized current valuesand the second fractionalized current values and to adjust the secondfractionalized current values to focus the second modulation field oneach location of a plurality of locations within the region of neuraltissue.
 10. The system of claim 9, wherein the neuromodulation generatoris configured to generate at least one sub-perception modulation fieldusing the electrodes, and at least one of the first modulation field andthe second modulation field is the sub-perception modulation field. 11.The system of claim 10, wherein the neuromodulation generator isconfigured to generate each of the first modulation field and the secondmodulation field as a sub-perception modulation field.
 12. The system ofclaim 10, wherein the neuromodulation generator is configured togenerate the first modulation field as a supra-perception field and togenerate the second modulation field as a sub-perception modulationfield.
 13. The system of claim 9, wherein the controller is configuredto adjust the first fractionalized current values to apply the firstmodulation field in a trolling fashion to cover the region of neuraltissue.
 14. The system of claim 9, wherein the controller is configuredto generate the first modulation field for a period of time beforegenerating the second modulation field.
 15. The system of claim 9,wherein the controller is configured to generate the first modulationfield for at least a portion of a time when the second modulation fieldis generated.
 16. The system of claim 9, wherein the controller isconfigured to: adjust the second fractionalized current values to focusthe second modulation field on each large location of a plurality oflarge locations, wherein the plurality of large locations is within theregion of neural tissue; and adjust the second fractionalized currentvalues to focus the second modulation field on each second locations ofthe plurality of small locations, wherein the plurality of smalllocations is within the each large location.
 17. A non-transitorycomputer-readable storage medium including instructions, which whenexecuted by a system, cause the system to perform a method fordelivering neuromodulation, the method comprising: generating a firstmodulation field over a region of neural tissue using electrodes andfirst fractionalized current values for the electrodes; generating asecond modulation field using the electrodes and second fractionalizedcurrent values for the electrodes; and adjusting the secondfractionalized current values to focus the second modulation field oneach location of a plurality of locations within the region of neuraltissue.
 18. The non-transitory computer-readable storage medium of claim17, wherein the first modulation field is a supra-perception field, andthe second modulation field is a sub-perception field.
 19. Thenon-transitory computer-readable storage medium of claim 17, wherein thefirst modulation field is applied in a trolling fashion to cover theregion of neural tissue.
 20. The non-transitory computer-readablestorage medium of claim 17, wherein the plurality of locationscomprises: a plurality of large locations; and a plurality of smalllocations within each large location of the plurality of largelocations, and adjusting the second fractionalized current values tofocus the second modulation field on each location of the plurality oflocations comprises: adjusting the second fractionalized current valuesto focus the second modulation field on each large location of theplurality of large locations; and adjusting the second fractionalizedcurrent values to focus the second modulation field on each secondlocations of the plurality of small locations within the each largelocation.